Proposed is a Tobacco Center of Regulatory Science (TCORS) for Research Relevant to the Family Smoking Prevention and Tobacco Control Act (FSPTCA). The proposed Center will characterize combustible and non-combustible, conventional, new and manipulated nicotine/tobacco products and the impact of variations in those products on human behavior and exposure. The focus of the Center is the products and resulting human use behaviors and exposures, examined in crossover acute laboratory trials. Objective 1. To characterize the chemical profiles and physical properties of combustible, non-combustible, conventional, new and manipulated tobacco products (Project I and Core B). Objective 2. To differentiate the appeal and consumer acceptance of combustible tobacco products that differ only on a single characteristic of interest (e.g., menthol concentration, smok pH) (Project II). Objective 3. To explore tobacco microbial constituents and the oral microbiome of tobacco users (Project III). Objective 4. To support the data management and statistical needs of the Center, and provide FDA CTP/NIH and select other Centers with early access to the data. Objective 5. To train the next generation of transdisciplinary scientists in science to inform tobacco regulation. Objective 6. To expand the knowledge base through a rapid response system of developmental/pilot projects. The results of the proposed research will provide scientific data to inform the regulation of tobacco products by the FDA Center for Tobacco Products (CTP). The proposed Center will address, at a minimum, two research priorities: 1) Diversity of Tobacco Products - understanding the constituents, components, ingredients, additives, and design features; use behaviors; 2)Adverse Health Consequences - understanding health risks of multiple tobacco types... RELEVANCE: In most studies, one can only examine a single dimension of tobacco harm. This is a proposal to simultaneously measure harm in three orthoganal contexts: toxicity, consumer accepance and liking, and bacterial exposure, providing a much clearer picture of where a product lies in a continuum of harm, and a scientific basis for regulation of particular product design features.